scholarly journals Implementation of vancomycin dosing nomogram in an electronic prescribing system: an innovative tool in antibiotic stewardship

2014 ◽  
Vol 50 (3) ◽  
pp. 567-572 ◽  
Author(s):  
Tácio de Mendonça Lima ◽  
Sabrina Calil Elias ◽  
Rita de Cássia Elias Estrela ◽  
Fernando Luiz Lopes Cardoso
Keyword(s):  
Electronic Prescribing ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Trough Serum ◽  
Serious Infections ◽  
Serum Trough ◽  
Dosing Regimens ◽  
Basic Parameters ◽  
Innovative Tool ◽  
Computer Based ◽  
Dosing Nomogram

Vancomycin (VAN) is the gold standard therapy for Methicillin-resistant Staphylococcus aureus(MRSA) infections such as bacteremia and endocarditis. However, VAN suboptimal dosing for serious infections caused by S. aureus isolates that have elevated minimum inhibitory concentration (MIC), could be associated with poor outcome. Better understanding of VAN pharmacokinetics and pharmacodynamics (PK/PD) has led to the creation of new recommendations with optimized dosing regimens for the treatment of MRSA infections. For severe infectious, such as pneumonia and endocarditis, a VAN serum trough concentration of 15-20 mg/L at the steady state should be targeted. The aim of this study was to show how a nomogram with updated VAN dosing was devised and how it was implemented in the electronic prescribing (e-prescribing) system of a teaching hospital. VAN loading dose and maintenance doses were calculated from a pharmacokinetic equation using basic parameters: weight, estimated creatinine clearance, as well as peak and trough serum concentrations. The implementation of the VAN dosing nomogram in the hospital e-prescribing system definitively changed the long-standing medical prescription fallacy of "same dose fits all". Finally, this computer-based electronic program has allowed a wide-ranging intervention and should be recognized as a powerful tool for implementation in antimicrobial stewardship programs.

scholarly journals Vancomycin Dosing in Healthy-Weight, Overweight, and Obese Pediatric Patients

2014 ◽  
Vol 19 (3) ◽  
pp. 182-188
Author(s):  
Lea S. Eiland ◽  
Kalyani B. Sonawane
Keyword(s):  
Serum Concentration ◽  
Pediatric Patients ◽  
Therapeutic Monitoring ◽  
Pharmacokinetic Parameters ◽  
Obese Patients ◽  
Healthy Weight ◽  
Serum Concentrations ◽  
Trough Serum Concentration ◽  
Trough Serum ◽  
Dosing Regimens

OBJECTIVES: With an increase in vancomycin resistance and the prevalence of obesity in children, alterations of vancomycin dosing regimens may be necessary to achieve target serum concentrations. The primary objective of this study was to describe initial vancomycin dosing with resulting serum concentrations in healthy-weight and overweight/obese children. Secondary objectives include comparing vancomycin dosing regimens of healthy-weight and overweight/obese patients that produced target trough serum concentrations and evaluating the likelihood of attaining target concentrations by patient characteristics. METHODS: This retrospective review evaluated healthy-weight and overweight/obese patients, aged 2 to 18 years, who had vancomycin trough serum concentrations obtained between 2005 and 2010. Vancomycin dosing, initial trough serum concentrations, pharmacokinetic parameters, and patient demographics were collected for analysis. Target trough serum concentrations were defined as 10 to 20 mg/L. RESULTS: The study included 98 patients (48 healthy weight, 50 overweight/obese) of which only 14 patients (14.2%, 6 healthy weight, 8 obese) reached a target trough serum concentration with empiric dosing. No difference was found between the mean daily dosing of vancomycin that produced target trough serum concentrations in healthy-weight or overweight/obese patients (53.63 mg/kg/day vs 51.6 mg/kg/day, respectively). Demographic or clinical characteristics were not found to be associated with the likelihood of target trough serum concentration attainment. CONCLUSIONS: Vancomycin dosing in healthy-weight and overweight/obese pediatric patients did not reach target trough serum concentrations most of the time. In obtaining initial target serum concentrations, no dosing difference was identified for overweight/obese patients compared with healthy-weight patients. Alternate dosing strategies, therapeutic monitoring, and clinical outcomes should continue to be evaluated in this population.

Home Therapy With Subcutaneous Immunoglobulin Infusions in Children With Congenital Immunodeficiencies

PEDIATRICS ◽  
1996 ◽  
Vol 98 (6) ◽  
pp. 1127-1131
Author(s):  
Tore G. Abrahamsen ◽  
Heidi Sandersen ◽  
Alfhild Bustnes
Keyword(s):  
Severe Combined Immunodeficiency ◽  
Immunoglobulin M ◽  
Subcutaneous Immunoglobulin ◽  
Home Therapy ◽  
Subcutaneous Infusion ◽  
Therapy Program ◽  
Trough Serum ◽  
Serious Infections ◽  
Syringe Driver ◽  
The Family

Objectives. Patients with congenital, humoral immunodeficiencies are usually treated with intravenous immunoglobulin infusions. Subcutaneous infusions have emerged as an alternative treatment modality also in children. Our institution has run a subcutaneous infusion home therapy program for 6 years, and the purpose of this report is to describe our experience with this regimen. Methods. The subcutaneous therapy of eight patients with immunodeficiency (three with agammaglobulinemia, one with common variable immunodeficiency, one with severe combined immunodeficiency and bone marrow transplantation, and three with hyper-immunoglobulin M syndrome) was evaluated by chart review and a questionnaire answered by all the families. The infusions were given for at least 3 hours each week by a small syringe driver at home after the family had attended an intensive educational course at the hospital. Results. The children were given a total of approximately 1100 infusions. They started at the age of 2 to 8 (mean, 4.5) years and received these infusions for 1.5 to 6 (mean, 3) years. By administering immunoglobulin doses from 58 to 149 (mean, 97) mg/kg per week, trough serum immunoglobulin G values from 5.2 to 9.6 (mean, 7) g/L were obtained. No serious infections occurred. Short-lasting, local side effects such as swelling and redness were frequently reported, but pain or systemic adverse reactions during or after the infusions were never encountered. Conclusions. Home therapy with subcutaneous immunoglobulin infusions in children with congenital immunodeficiencies is a feasible and safe treatment alternative.

Pharmacokinetics and pharmacodynamics of six epoetin alfa dosing regimens in anemic critically ill patients without acute blood loss*

2009 ◽  
Vol 37 (4) ◽  
pp. 1299-1307 ◽  
Author(s):  
Alejandro C. Arroliga ◽  
Kalpatha K. Guntupalli ◽  
Jessica S. Beaver ◽  
Wayne Langholff ◽  
Kimberly Marino ◽  
...  
Keyword(s):  
Blood Loss ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Acute Blood Loss ◽  
Epoetin Alfa ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dosing Regimens

Attributable nephrotoxicity of vancomycin in critically ill patients: a marginal structural model study

2020 ◽  
Vol 75 (4) ◽  
pp. 1031-1037 ◽  
Author(s):  
Frederico Carlos de Sousa Arnaud ◽  
Alexandre Braga Libório
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Structural Model ◽  
Trough Level ◽  
Kidney Injury ◽  
Serum Levels ◽  
Marginal Structural Model ◽  
Model Study ◽  
Trough Serum ◽  
Serum Trough

Abstract Background Although vancomycin nephrotoxicity is recognizable, critically ill patients have other potential reasons for acute kidney injury (AKI) and determining its attributable nephrotoxic risk in this population can be cumbersome. Objectives To determine the risk of AKI attributable to vancomycin, controlling for baseline and time-dependent confounders. Methods Time-fixed and daily time-varying variables were extracted from a large public database. The exposures analysed were: (i) IV vancomycin; (ii) serum trough level greater than 15 and 20 mg/L; and (iii) concomitant exposure to vancomycin and piperacillin/tazobactam or other antipseudomonal β-lactams. Censoring and exposure inverse probability of treatment weighting were calculated. Marginal structural models were plotted to evaluate AKI, severe AKI (stage 2/3) and need of renal replacement therapy (RRT). Results A total of 26 865 patients were included; 19.7% received vancomycin during ICU stay. After adjusting for fixed and time-variable confounders, vancomycin exposure was associated with AKI (HR = 1.24, 95% CI = 1.09–1.38), but not with severe AKI or need of RRT (HR = 1.05, 95% CI = 0.91–1.23 and HR = 0.97, 95% CI = 0.74–1.29, respectively). A serum trough level greater than 20 mg/L was associated with AKI (HR = 1.90, 95% CI = 1.52–2.30) and severe AKI (HR = 1.69, 95% CI = 1.31–2.19), but showed no statistically significant association with need of RRT (HR = 1.48, 95% CI = 0.92–2.56). The vancomycin + piperacillin/tazobactam combination was not associated with a greater risk than vancomycin alone. Conclusions The attributable nephrotoxicity of vancomycin in critically ill patients is significantly lower than previously suggested and severe AKI is related to vancomycin only when trough serum levels are greater than 20 mg/L.

Oblimersen can be administered by subcutaneous (SC) and brief intravenous (IV) infusion: Clinical pharmacokinetics and pharmacodynamics (PK/PD) in patients with advanced cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14083-14083
Author(s):  
C. Lin ◽  
K. Papadopoulos ◽  
A. Patnaik ◽  
K. Sankhala ◽  
C. H. Takimoto ◽  
...  
Keyword(s):  
Compartmental Analysis ◽  
Dose Proportionality ◽  
Continuous Intravenous Infusion ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dose Escalation Study ◽  
Peripheral Blood Mononuclear ◽  
Clinical Pharmacokinetics ◽  
Protein Levels ◽  
Dosing Regimens ◽  
Dose Ranging

14083 Background: Oblimersen (OBL) is a phosphorothioate oligodeoxynucleotide that decreases Bcl-2 protein levels. OBL has been administered by continuous intravenous infusion (CIVI) in most clinical studies. However, recent preclinical data suggest that equivalent or superior antitumor efficacy can be achieved with intermittent administration. We conducted a dose-ranging PK/PD study of OBL given by bolus SC injection and brief IV infusion to evaluate the feasibility of intermittent dosing. Methods: In this within-subject dose-escalation study, OBL was administered subcutaneously (SC) at doses of 75, 150 and 225 mg. In part II of the study, OBL was administered by 2-hr IV infusion beginning at 150 mg on day 1, by single-dose SC injection on day 8, and 2-hr IV daily x 5 consecutive days. Pharmacokinetics were assessed by non-compartmental analysis. Pharmacodynamic measurements of Bcl-2 levels in peripheral blood mononuclear (PBM) cells were made using Western blot analysis. Results: OBL absorption after SC administration was rapid with a Tmax of ∼2 hours. Mean Cmax values were 0.76, 1.70 and 3.10 μg/ml for the 75, 150 and 225 mg SC doses, respectively. Mean AUC0- inf values were 7.78, 15.36 and 25.57 hr*μg/mL. Plots of dose-normalized Cmax and AUC vs. dose showed slopes close to zero, indicating approximate dose proportionality. AUC0–24 exposure with the 225 mg SC dose was similar to previously established 24-hr steady-state AUCs after 3 mg/kg CIVI. SC injection was associated with an inflammatory erythematous grade 1 rash at the injection site that resolved within 7 days. The 150 mg 2-hr IV infusion x 1 or daily x 5 has been well-tolerated. Conclusions: OBL exposure from a single SC injection is similar to a 24-hr 3 mg/kg CIVI, and the 2-hr IV infusion is currently being evaluated. Both schedules appear to be well- tolerated, may reduce requirements for CIVI, and could be incorporated into intermittent dosing regimens. No significant financial relationships to disclose.

scholarly journals 734. Modeling the Pharmacokinetics and Pharmacodynamics of Intravenous and Oral Omadacycline with and without a Loading Dose

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S329-S329
Author(s):  
Lawrence Friedrich ◽  
Marla Curran ◽  
Surya Chitra ◽  
Amy Manley ◽  
Stephen Bai ◽  
...  
Keyword(s):  
Steady State ◽  
Bacterial Pneumonia ◽  
Phase 1 ◽  
The United States ◽  
Clinical Impact ◽  
Loading Dose ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dosing Regimens ◽  
The Impact

Abstract Background Omadacycline (OMC) is an intravenous (IV) and oral aminomethylcycline antibiotic in the tetracycline class approved in the United States to treat acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP) in adults. The approved dosing regimens of OMC include a loading dose designed to achieve steady-state exposures early in the course of therapy. We assessed the impact on OMC exposure and subsequent pharmacodynamics (PD) on Day 2 and at steady state (Day 5) in the situation where a loading dose may not be given. Methods Phase 1 pharmacokinetic (PK) data were used to determine OMC exposure on Day 2 and at steady state (Day 5) for the following: IV regimens 100 mg IV q12h on Day 1 then 100 mg IV QD (load), 100 mg IV QD (no load); and oral regimens 450 mg oral QD on Days 1 and 2 then 300 mg QD (load) and 300 mg oral QD (no load). AUCs on Day 2 and Day 5 for no-load regimens were compared with the regimens with loading doses. Additionally, AUC:MIC ratios were calculated using OMC MIC90 for two main pathogens of interest in ABSSSI and CABP, respectively, Staphylococcus aureus (0.25 mg/L) and Streptococcus pneumoniae (0.12 mg/L). In vivo AUC:MIC targets for stasis and 1-log kill used were 21.9 and 57.7 (S. aureus) and 31.2 and 65.8 (S. pneumoniae). Results Day 2 and 5 AUCs are shown in the Figure. AUCs on Day 2 were lower for the two regimens without loading doses and were 72% (IV) and 73% (oral) of those with a loading dose. However, at steady state on Day 5, no-load regimen AUCs were essentially the same at 98% for both the IV and oral regimens. Despite lower AUCs on Day 2 for the no-load regimens, the AUC:MIC ratio would still be expected to exceed the stasis threshold for both pathogens and the 1-log kill threshold for S. pneumoniae (figure). This same pattern was also noted on Day 5. Conclusion Exposure as assessed using AUC was lower early on in therapy on Day 2 for both IV and oral regimens. However, exposures were not different on Day 5 at steady state. Despite lower exposure on Day 2, OMC would still be expected to meet or exceed PK/PD thresholds associated with stasis for S. aureus and S. pneumoniae. The 1-log kill threshold was exceeded for S. pneumoniae. Further studies are needed to confirm any clinical impact of the omission of OMC loading doses. Disclosures All authors: No reported disclosures.

scholarly journals Pharmacokinetic and Pharmacodynamic Profiles of Danofloxacin Administered by Two Dosing Regimens in Calves Infected with Mannheimia (Pasteurella) haemolytica

2002 ◽  
Vol 46 (9) ◽  
pp. 3013-3019 ◽  
Author(s):  
Patxi Sarasola ◽  
Peter Lees ◽  
Fariborz Shojaee AliAbadi ◽  
Quintin A. McKellar ◽  
William Donachie ◽  
...  
Keyword(s):  
Area Under The Curve ◽  
Pasteurella Haemolytica ◽  
Bolus Administration ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Blood Samples ◽  
Bronchial Secretions ◽  
Lung Consolidation ◽  
Time Period ◽  
High Maximum ◽  
Dosing Regimens

ABSTRACT The pharmacokinetics and pharmacodynamics of danofloxacin in calves with induced Mannheimia (Pasteurella) haemolytica pneumonia were evaluated. Calves received either saline as an intravenous (IV) bolus or danofloxacin (0.738 mg/kg of body weight) administered as either a single IV bolus or a 36-h continuous IV infusion. Blood samples and bronchial secretions were collected before and at predetermined times over 48 h following the start of treatment. Calves were assessed clinically throughout, and lung consolidation was assessed at necropsy. Bronchial secretions and lung tissue were cultured for M. haemolytica. Bolus administration of danofloxacin produced a high maximum drug concentration-to-MIC ratio (C max:MIC) of 14.5 and a time period of 9.1 h when plasma danofloxacin concentrations exceeded the MIC (T>MIC). Following danofloxacin infusion, the C max:MIC was low (2.3), with a long T>MIC (33.3 h). The area under the curve-to-MIC ratios were 43.3 and 49.1 for the bolus and infusion administrations, respectively. The single bolus of danofloxacin was more effective than the same dose administered by continuous infusion, as indicated by a significantly lower (P < 0.05) number of animals with M. haemolytica in bronchial secretions after treatment and lower rectal temperatures in the 24 h after the start of treatment. Thus, danofloxacin exhibited concentration-dependent antimicrobial activity in cattle with respiratory disease caused by M. haemolytica.

scholarly journals Disposition and bioavailability of ceftazidime after intraperitoneal administration in patients receiving continuous ambulatory peritoneal dialysis.

1996 ◽  
Vol 7 (11) ◽  
pp. 2399-2402 ◽  
Author(s):  
S Stea ◽  
T Bachelor ◽  
M Cooper ◽  
P de Souza ◽  
K Koenig ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
High Performance ◽  
Intraperitoneal Administration ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Standard Regimen ◽  
Drug Concentrations ◽  
Trough Serum ◽  
Dosing Regimens

This study investigated the disposition and bioavailability of ceftazidime when it was given intraperitoneally. Seven patients were given 1 gm of ceftazidime intravenously, and 1 wk later, the same dose was given intraperitoneally. After both intravenous and intraperitoneal dosing, serum and peritoneal dialysate samples were obtained at set time intervals over a 24-h period. High-performance liquid chromatography was used to determine the ceftazidime concentrations in the serum and dialysate samples. Inspection of the concentration versus time data after intraperitoneal dosing demonstrated that serum ceftazidime concentrations reached therapeutic (> 8 micrograms/mL) levels within 30 min and remained in the therapeutic range for the entire 24-h period. Simulation of a variety of ceftazidime dosing regimens using the mean pharmacokinetic parameters from this population of patients suggests that a regimen of 1.5 gm administered intraperitoneally every 24 h produces trough serum drug concentrations (approximately 40 micrograms/mL) similar to those achieved with a standard regimen of 1.0 gm given intravenously every 24 h in patients undergoing continuous ambulatory peritoneal dialysis. It was concluded that the intraperitoneal dosing of ceftazidime in these patients is an equally effective and a more convenient alternative to its administration.

Pharmacokinetic and pharmacodynamic principles of antimicrobials

2016 ◽  
Author(s):  
Menino Osbert Cotta ◽  
Jason Roberts
Keyword(s):  
Antimicrobial Resistance ◽  
Protein Binding ◽  
Clinical Outcomes ◽  
Antimicrobial Therapy ◽  
Potential Role ◽  
Volume Of Distribution ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dosing Regimens ◽  
Dosing Strategies

The continual threat of antimicrobial resistance means that optimizing current antimicrobial therapy is of paramount importance. Antimicrobial pharmacokinetics and pharmacodynamics (PK/PD) play a central role in developing dosing regimens that target maximal clinical outcomes and microbiological eradication. This chapter describes the three main PK/PD indices into which current antimicrobials are categorized. Elements of PK that require due consideration when optimizing antimicrobial therapy, including volume of distribution, antimicrobial clearance, and protein binding, are also discussed. Finally, specific attention is paid to antimicrobial dosing among challenging populations, namely the critically ill and obese, and the potential role of alternative dosing strategies, such as use of loading doses and extended/continuous infusions, is also outlined.

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